The use of oral aCD3 Monoclonal antibody (MAb) alone in subjects with hepatitis C is justified on the basis of scientific and medical reasons. There are data in multiple animal models that aCD3-alone confers efficacy in models of inflammatory or autoimmune disease and induces regulatory T cells and immune-modulation as desired in clinical studies. These observations are reinforced by data in the Phase 1 clinical study showing that aCD3-alone induced the desired immune-modulation in terms of immunological markers for regulatory T cells and appropriate rises and declines in certain cytokine levels.

This clinical study is designed to evaluate as Primary Objective the safety of oral administration of the study drug anti-CD3 MAb to non responder genotype I subjects with the chronic Hepatitis C. [ Time Frame: 60 ] [ Designated as safety issue: Yes ]

The safety and tolerability of oral administration of the study drug cocktail will be evaluated at Days 7, 14, 21 and 30 by physical examinations and thorough medical history and laboratory evaluations as described below and by the subject through his/her diary entries. In addition, subjects will be assessed for safety at Day 60

Secondary Outcome Measures:

Decrease in the concentration of HCV [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Oral anti-CD3 MAb will be administered at a dosage level of 0.2 or 1.0 or 5.0 mg per day for 30 days. Up to 9 subjects will be treated at each dosage level

Drug: anti-CD3 monoclonal antibody

Oral anti-CD3 MAb will be administered at a dosage level of 0.2 or 1.0 or 5.0 mg per day for 30 days. One 20mg tablet of Omeprazole (a proton pump inhibitor) will be taken concomitantly orally

Placebo Comparator: Sodium chloride

Up to 9 subjects will receive placebo. Subjects will receive the drug in a similar manner as as the treatment group

Drug: Sodium Chloride placebo

Sodium chloride will be administered orally every day for 30 days. Up to 9 subjects will be treated at each dosage level. One 20mg tablet of Omeprazole (a proton pump inhibitor) will be taken concomitantly orally

Detailed Description:

Oral aCD3 MAb will be administered at a dosage level of 0.2 or 1.0 or 5.0 mg per day for 30 days. Up of 9 subjects will be treated at each dosage level, and up to 9 subjects will receive placebo buffered in normal saline that is used as diluents for the MAb. One 20mg tablet of Omeprazole (a proton pump inhibitor) will be taken orally as part of the study drug cocktail in order to neutralize stomach pH for enhancing stability of the MAb. During the treatment period, subjects will ingest the study drug/s every day for 30 days, and will be followed for clinical and laboratory effects. Subjects will be followed up to Day 60 (30 days after termination of treatment)

Eligibility

Ages Eligible for Study:

18 Years to 65 Years (Adult)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Subjects who have completed the informed consent process culminating with written informed consent by the subject.

Men and women age 18 to 65 years (inclusive).

Diagnosis of chronic active HCV infection was based on liver biopsy (within 3 years of initiation of study),

Patients who failed treatment with Interferon or Peg-Interferon and Ribavirin (<2-log change in HCV level during the 12 weeks of treatment)

HCV RNA in blood for at Screening Visit, ≥600 copies/mL

Abstinence from any alternative medications or vitamin-D-containing supplements for three months prior to initiation of therapy was stipulated.

Subjects who have been treated with any type of immune modulatory drug including systemic steroids or NSAID within the last 4 weeks.

Subjects who have received either methotrexate or cyclosporine or anti-TNF (infliximab, Remicade) or anti-integrin (namixilab) at any time or who have participated in any other clinical trial within the last 3 months.

Subjects who will be unavailable for the duration of the trial, who are unlikely to be compliant with the protocol, or who are felt to be unsuitable by the Investigator for any other reason.

Subjects who are HIV-positive.

Subjects who are positive for anti-HBcAg

Subjects with active CMV infection.

Subjects with autoimmune hepatitis

Subjects with IgG anti-cardiolipin antibody >16 IU.

Any prior exposure to anti-CD3 MAb.

Known sensitivity to any ingredients in the study drug

Any know autoimmune disease except for the studied disorders

Subjects with excess alcohol use (> 30 g/day)

Subjects with drug addiction based on the physician's judgment

Subjects with TSH >6 mIU/L

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01459419